Genotype-by-environment (G × E) interaction is a cornerstone concept in genetic improvement, crucial for enhancing crop yield stability under diverse conditions. This chapter reviews the evolution of G × E research from early agronomic studies and classical statistical models to sophisticated genomic and computational approaches. Major developments include the introduction of bilinear models, the integration of molecular markers, and the use of simulation models to dissect trait components. Key examples illustrate G × E’s impact on crops such as wheat, maize, cowpea, and quinoa, addressing traits like grain yield, plant height, flowering time, disease resistance, and grain quality. Despite significant advances, research gaps persist, notably in understanding abiotic stress-related G × E causes and in the underrepresentation of orphan crops like amaranth and millet. While biotic stress causes have been more thoroughly characterized, abiotic factors demand finer-scale environmental characterization. Furthermore, studies remain heavily skewed toward Old World cereal crops, leaving pulse, oilseed, and pseudocereal native American crops less explored. Looking ahead, the future of G × E research lies in integrating genotyping, phenotyping, and envirotyping with artificial intelligence and predictive models. Emphasis on climate-resilient breeding, targeted multi-environment trials, and broader crop diversification is essential to ensure global food security in a rapidly changing environment.